A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene (AURORA)
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| ClinicalTrials.gov Identifier: NCT04123626 |
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Recruitment Status :
Active, not recruiting
First Posted : October 11, 2019
Last Update Posted : May 6, 2022
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Sponsor:
ProQR Therapeutics
Information provided by (Responsible Party):
ProQR Therapeutics
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Brief Summary:
This study evaluates the safety, tolerability and efficacy of QR-1123 injection in the eye (intravitreal; IVT) injections (one eye/unilateral) in subjects receiving a single dose or repeat doses. Single injections will be assessed in an open label way, and repeat injections will be assessed in a double-masked, randomized, sham-controlled fashion.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Autosomal Dominant Retinitis Pigmentosa Eye Diseases Eye Diseases, Hereditary Retinal Dystrophies Retinal Disease Retinitis Vision Tunnel Vision Disorders | Drug: QR-1123 Other: Sham procedure | Phase 1 Phase 2 |
QR-1123 is an antisense oligonucleotide, designed to specifically target the mutant P23H messenger ribonucleic acid (mRNA) in order to reduce the expression of the P23H protein selectively, while preserving expression of the wild type (WT) rhodopsin (RHO) protein. It is hypothesized that the reduction of mutant P23H mRNA will reduce the deleterious effects of the dominant-negative protein and should result in increased function of WT rhodopsin protein in photoreceptors. Restoration of WT RHO function is expected to improve vision in patients with adRP due to the P23H mutation.
The study will comprise up to 8 single dose and repeat dose cohorts. Prior to initiating a higher single dose cohort and/or prior to initiating repeat dose cohort(s), available safety and efficacy data will be reviewed by the DMC.
In the single dose cohorts subjects will receive a single, unilateral IVT injection of QR-1123 in an open label fashion. In the repeat dose cohorts subjects will be randomized to receive either a unilateral IVT injection of QR-1123 every 3 months or a unilateral sham procedure every 3 months, in a double masked fashion. Subjects will be followed for safety, tolerability and efficacy for a total period of 12 months.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 11 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | Triple (Participant, Care Provider, Outcomes Assessor) |
| Masking Description: | Single dose cohorts are open label. Repeat dose cohorts are randomized, double masked. |
| Primary Purpose: | Treatment |
| Official Title: | A Prospective First-In-Human Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa (adRP) Due to the P23H Mutation in the RHO Gene |
| Actual Study Start Date : | October 7, 2019 |
| Estimated Primary Completion Date : | June 7, 2022 |
| Estimated Study Completion Date : | June 7, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Retinitis pigmentosa
Lenz microphthalmia syndrome
Oculofaciocardiodental syndrome
MedlinePlus related topics:
Genes and Gene Therapy
| Arm | Intervention/treatment |
|---|---|
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Experimental: QR-1123 Single dose - dose level 1
Open label Single dose cohort: dose level 1
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Drug: QR-1123
unilateral IVT injection |
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Experimental: QR-1123 Single dose - dose level 2
Open label Single dose cohort: dose level
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Drug: QR-1123
unilateral IVT injection |
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Experimental: QR-1123 Single dose - dose level 3
Open label Single dose cohort: dose level 3
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Drug: QR-1123
unilateral IVT injection |
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Experimental: QR-1123 Single dose - dose level 4
Open label Single dose cohort: dose level 4
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Drug: QR-1123
unilateral IVT injection |
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Experimental: QR-1123 Single dose - dose level 5
Open label Single dose cohort: dose level 5
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Drug: QR-1123
unilateral IVT injection |
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Experimental: Repeat dose cohort 1
Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data.
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Drug: QR-1123
unilateral IVT injection Other: Sham procedure Sham procedures (i.e. no penetration of the globe) closely mimic the active injection and serve to mask subjects to treatment assignment |
Primary Outcome Measures :
- Incidence and Severity of ocular AEs [ Time Frame: up to 12 months ]Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye
- Incidence and Severity of non-ocular AEs [ Time Frame: up to 12 months ]Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye
Secondary Outcome Measures :
- Changes in BCVA [ Time Frame: up to 12 months ]Changes in Best corrected visual acuity (BCVA)
- Changes in LLVA [ Time Frame: up to 12 months ]Changes in Low-luminance visual acuity (LLVA)
- Changes in DAC perimetry [ Time Frame: up to 12 months ]Changes in Dark adapted chromatic (DAC) perimetry
- Changes in Static VF [ Time Frame: up to 12 months ]Changes in Static VF (Visual Field)
- Changes in Microperimetry [ Time Frame: up to 12 months ]Changes in Microperimetry
- Changes in SD-OCT [ Time Frame: up to 12 months ]Changes in Spectral Domain-Optical Coherence Tomography
- Changes in FST [ Time Frame: up to 12 months ]Changes in Full-field Stimulus Threshold (FST)
- Changes in Full-field ERG [ Time Frame: up to 12 months ]Changes in Full-field Electroretinogram (ERG)
- Assessment of systemic exposure after treatment with QR-1123 [ Time Frame: up to 12 months ]Serum levels of QR-1123
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Main Inclusion Criteria:
- Male or female, ≥ 18 years of age.
- Clinical presentation consistent with adRP, based on ophthalmic examinations.
- Impairment on VF in the opinion of the Investigator, as determined by perimetry.
- A molecular diagnosis of autosomal dominant form of RP with the P23H mutation in the RHO gene, based on genetic analysis.
- A clear ocular media and adequate pupillary dilation to permit good quality fundus imaging, as assessed by the Investigator.
Main Exclusion Criteria:
- Presence of additional pathogenic mutations in genes (other than the P23H mutation in the RHO gene) associated with inherited retinal degenerative diseases or syndromes, based on genetic analysis (eg, Usher syndrome, Leber congenital amaurosis, etc).
- Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04123626
Locations
| United States, Colorado | |
| Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology | |
| Aurora, Colorado, United States, 80045 | |
| United States, Florida | |
| VitreoRetinal Associates | |
| Gainesville, Florida, United States, 32607 | |
| United States, Kentucky | |
| Shriners UK Ophthalmology - University of Kentucky | |
| Lexington, Kentucky, United States, 40536 | |
| United States, Oregon | |
| Casey Eye Institute, OHSU | |
| Portland, Oregon, United States, 97239 | |
| United States, Texas | |
| Retina Foundation of the Southwest | |
| Dallas, Texas, United States, 75231 | |
Sponsors and Collaborators
ProQR Therapeutics
Investigators
| Study Director: | ProQR Medical Monitor | ProQR Therapeutics | |
| Study Director: | ProQR Clinical Trial Manager | ProQR Therapeutics |
| Responsible Party: | ProQR Therapeutics |
| ClinicalTrials.gov Identifier: | NCT04123626 |
| Other Study ID Numbers: |
PQ-1123-001 |
| First Posted: | October 11, 2019 Key Record Dates |
| Last Update Posted: | May 6, 2022 |
| Last Verified: | May 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by ProQR Therapeutics:
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adRP Retinitis Pigmentosa P23H mutation Rhodopsin |
antisense oligonucleotide IVT autosomal dominant |
Additional relevant MeSH terms:
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Arthrogryposis Vision Disorders Eye Diseases Retinitis Retinitis Pigmentosa Retinal Diseases Retinal Dystrophies Eye Diseases, Hereditary Genetic Diseases, Inborn |
Retinal Degeneration Joint Diseases Musculoskeletal Diseases Muscular Diseases Musculoskeletal Abnormalities Congenital Abnormalities Sensation Disorders Neurologic Manifestations Nervous System Diseases |